@article{RN3210,

title = {Quantum dots in diagnostics and detection: principles and paradigms},

author = { T. R. 2nd Pisanic and Y. Zhang and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24770716},

doi = {10.1039/c4an00294f},

issn = {1364-5528 (Electronic) 

0003-2654 (Linking)},

year  = {2014},

date = {2014-06-21},

journal = {Analyst},

volume = {139},

number = {12},

pages = {2968-81},

abstract = {Quantum dots are semiconductor nanocrystals that exhibit exceptional optical and electrical behaviors not found in their bulk counterparts. Following seminal work in the development of water-soluble quantum dots in the late 1990's, researchers have sought to develop interesting and novel ways of exploiting the extraordinary properties of quantum dots for biomedical applications. Since that time, over 10,000 articles have been published related to the use of quantum dots in biomedicine, many of which regard their use in detection and diagnostic bioassays. This review presents a didactic overview of fundamental physical phenomena associated with quantum dots and paradigm examples of how these phenomena can and have been readily exploited for manifold uses in nanobiotechnology with a specific focus on their implementation in in vitro diagnostic assays and biodetection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3215,

title = {Droplet Array Platform for High-Resolution Melt Analysis of DNA Methylation Density},

author = { P. Athamanolap and D. J. Shin and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24114798},

doi = {10.1177/2211068213507923},

issn = {2211-0690 (Electronic) 

2211-0682 (Linking)},

year  = {2014},

date = {2014-06-01},

journal = {J Lab Autom},

volume = {19},

number = {3},

pages = {304-12},

abstract = {High-resolution melting (HRM) has garnered significant interest as an analytical technique for a number of applications, including DNA methylation detection, due to its inherent sensitivity and robustness. In this study, we describe a miniaturized assay platform for quantitative methylation density analysis using a microfluidic droplet array cartridge. We demonstrate that the DNA methylation level of the RASSF1A promoter can be directly analyzed using HRM. PCR products were generated by amplifying bisulfite-treated DNA with varying CpG densities using CpG island-flanking primer sets. Subsequent HRM analysis on the miniaturized droplet platform shows distinct melting curve profiles associated with methylation levels, which was verified using a conventional benchtop PCR-HRM system. The characteristic melting temperature (Tm) of the PCR products was used to directly quantify the respective levels of DNA methylation density. Our approach provides a key advantage over current gold standard methods such as methylation-specific PCR (MSP), which are incapable of providing specific information regarding the overall methylation density of the target genes. The miniaturized platform establishes a practical approach to methylation density profiling from multiple DNA samples with a potential application in point-of-care diagnostics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3211,

title = {Elimination of ligation dependent artifacts in T4 RNA ligase to achieve high efficiency and low bias microRNA capture},

author = { Y. Song and K. J. Liu and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24722341},

doi = {10.1371/journal.pone.0094619},

issn = {1932-6203 (Electronic) 

1932-6203 (Linking)},

year  = {2014},

date = {2014-04-12},

journal = {PLoS One},

volume = {9},

number = {4},

pages = {e94619},

abstract = {Adapter ligation is a critical first step in many microRNA analysis methods including microarray, qPCR, and sequencing. Previous studies have shown that ligation bias can have dramatic effects on both the fidelity of expression profiles and reproducibility across samples. We have developed a method for high efficiency and low bias microRNA capture by 3' adapter ligation using T4 RNA ligase that does not require pooled adapters. Using a panel of 20 microRNA, we investigated the effects of ligase type, PEG concentration, ligase amount, adapter concentration, incubation time, incubation temperature, and adapter design on capture efficiency and bias. Of these factors, high PEG% was found to be critical in suppressing ligation bias. We obtained high average capture efficiency and low CV across the 20 microRNA panel, both in idealized buffer conditions (86% +/- 10%) and total RNA spiking conditions (64% +/- 17%). We demonstrate that this method is reliable across microRNA species that previous studies have had difficulty capturing and that our adapter design performs significantly better than the common adapter designs. Further, we demonstrate that the optimization methodology must be specifically designed for minimizing bias in order to obtain the ideal reaction parameters.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3213,

title = {Large enhancement of quantum dot fluorescence by highly scalable nanoporous gold},

author = { L. Zhang and Y. Song and T. Fujita and Y. Zhang and M. Chen and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24339211},

doi = {10.1002/adma.201304503},

issn = {1521-4095 (Electronic) 

0935-9648 (Linking)},

year  = {2014},

date = {2014-02-26},

journal = {Adv Mater},

volume = {26},

number = {8},

pages = {1289-94},

abstract = {Dealloyed nanoporous gold (NPG) dramatically enhances quantum dot (QD) fluorescence by amplifying near-field excitation and increasing the radiative decay rate. Originating from plasmonic coupling, the fluorescence enhancement is highly dependent upon the nanopore size of the NPG. In contrast to other nanoengineered metallic structures, NPG exhibits fluorescence enhancement of QDs over a large substrate surface.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3212,

title = {Pressure induced lung injury in a novel in vitro model of the alveolar interface: protective effect of dexamethasone},

author = { D. D. Nalayanda and W. B. Fulton and P. M. Colombani and T. H. Wang and F. Abdullah},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24439582},

doi = {10.1016/j.jpedsurg.2013.09.030},

issn = {1531-5037 (Electronic) 

0022-3468 (Linking)},

year  = {2014},

date = {2014-01-01},

journal = {J Pediatr Surg},

volume = {49},

number = {1},

pages = {61-5; discussion 65},

abstract = {PURPOSE: The lungs of infants born with congenital diaphragmatic hernia suffer from immaturity as well as the short and long term consequences of ventilator-induced lung injury, including chronic lung disease. Antenatal and postnatal steroids are among current strategies promoted to treat premature lungs and limit long term morbidity. Although studied in whole-animal models, insight into ventilator-induced injury at the alveolar-capillary interface as well as the benefits of steroids, remains limited. The present study utilizes a multi-fluidic in vitro model of the alveolar-interface to analyze membrane disruption from compressive aerodynamic forces in dexamethasone-treated cultures. METHODS: Human alveolar epithelial cell lines, H441 and A549, were cultured in a custom-built chamber under constant aerodynamic shear followed by introduction of pressure stimuli with and without dexamethasone (0.1muM). On-chip bioelectrical measurements were noted to track changes to the cellular surface and live-dead assay to ascertain cellular viability. RESULTS: Pressure-exposed alveolar cultures demonstrated a significant drop in TEER that was less prominent with an underlying extracellular-matrix coating. Addition of dexamethasone resulted in increased alveolar layer integrity demonstrated by higher TEER values. Furthermore, dexamethasone-treated cells exhibited faster recovery, and the effects of pressure appeared to be mitigated in both cell types. CONCLUSION: Using a novel in vitro model of the alveolus, we demonstrate a dose-response relationship between pressure application and loss of alveolar layer integrity. This effect appears to be alleviated by dexamethasone and matrix sub-coating.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3214,

title = {Serial dilution via surface energy trap-assisted magnetic droplet manipulation},

author = { Y. Zhang and D. J. Shin and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24162777},

doi = {10.1039/c3lc50915j},

issn = {1473-0189 (Electronic) 

1473-0189 (Linking)},

year  = {2013},

date = {2013-12-21},

journal = {Lab Chip},

volume = {13},

number = {24},

pages = {4827-31},

abstract = {This paper demonstrates a facile method of generating precise serial dilutions in the form of droplets on an open surface platform. The method relies on the use of surface energy traps (SETs), etched areas of high surface energy on a Teflon coated glass substrate, to assist in the magnetic manipulation of droplets to meter and dispense liquid of defined volumes for the preparation of serial dilutions. The volume of the dispensed liquid can be precisely controlled by the size of the SETs, facilitating generation of concentration profiles of high linearity. We have applied this approach to the generation of serial dilutions of antibiotics for anti-microbial susceptibility testing (AST).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3220,

title = {Topography-assisted electromagnetic platform for blood-to-PCR in a droplet},

author = { C. H. Chiou and D. J. Shin and Y. Zhang and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23835223},

doi = {10.1016/j.bios.2013.06.011},

issn = {1873-4235 (Electronic) 

0956-5663 (Linking)},

year  = {2013},

date = {2013-12-15},

journal = {Biosens Bioelectron},

volume = {50},

pages = {91-9},

abstract = {This paper presents an electromagnetically actuated platform for automated sample preparation and detection of nucleic acids. The proposed platform integrates nucleic acid extraction using silica-coated magnetic particles with real-time polymerase chain reaction (PCR) on a single cartridge. Extraction of genomic material was automated by manipulating magnetic particles in droplets using a series of planar coil electromagnets assisted by topographical features, enabling efficient fluidic processing over a variety of buffers and reagents. The functionality of the platform was demonstrated by performing nucleic acid extraction from whole blood, followed by real-time PCR detection of KRAS oncogene. Automated sample processing from whole blood to PCR-ready droplet was performed in 15 min. We took a modular approach of decoupling the modules of magnetic manipulation and optical detection from the device itself, enabling a low-complexity cartridge that operates in tandem with simple external instruments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3216,

title = {Novel methylation biomarker panel for the early detection of pancreatic cancer},

author = { J. M. Yi and A. A. Guzzetta and V. J. Bailey and S. R. Downing and L. Van Neste and K. B. Chiappinelli and B. P. Keeley and A. Stark and A. Herrera and C. Wolfgang and E. P. Pappou and C. A. Iacobuzio-Donahue and M. G. Goggins and J. G. Herman and T. H. Wang and S. B. Baylin and N. Ahuja},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24088737},

doi = {10.1158/1078-0432.CCR-12-3224},

issn = {1078-0432 (Print) 

1078-0432 (Linking)},

year  = {2013},

date = {2013-12-01},

journal = {Clin Cancer Res},

volume = {19},

number = {23},

pages = {6544-6555},

abstract = {PURPOSE: Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here, we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer. EXPERIMENTAL DESIGN: We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum. RESULTS: We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreatic cancers (n = 143), up to 100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n = 42) from patients with pancreatic cancer, with a sensitivity for BNC1 of 79% [95% confidence interval (CI), 66%-91%] and for ADAMTS1 of 48% (95% CI, 33%-63%), whereas specificity was 89% for BNC1 (95% CI, 76%-100%) and 92% for ADAMTS1 (95% CI, 82%-100%). Overall sensitivity using both markers is 81% (95% CI, 69%-93%) and specificity is 85% (95% CI, 71%-99%). CONCLUSIONS: Promoter DNA methylation of BNC1 and ADAMTS1 is a potential biomarker to detect early-stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early detection of pancreatic cancer and has the potential to improve mortality from this disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3218,

title = {Extraction and processing of circulating DNA from large sample volumes using methylation on beads for the detection of rare epigenetic events},

author = { B. Keeley and A. Stark and T. R. 2nd Pisanic and R. Kwak and Y. Zhang and J. Wrangle and S. Baylin and J. Herman and N. Ahuja and M. V. Brock and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23911908},

doi = {10.1016/j.cca.2013.07.023},

issn = {1873-3492 (Electronic) 

0009-8981 (Linking)},

year  = {2013},

date = {2013-10-21},

journal = {Clin Chim Acta},

volume = {425},

pages = {169-75},

abstract = {The use of methylated tumor-specific circulating DNA has shown great promise as a potential cancer biomarker. Nonetheless, the relative scarcity of tumor-specific circulating DNA presents a challenge for traditional DNA extraction and processing techniques. Here we demonstrate a single tube extraction and processing technique dubbed "methylation on beads" that allows for DNA extraction and bisulfite conversion for up to 2 ml of plasma or serum. In comparison to traditional techniques including phenol chloroform and alcohol extraction, methylation on beads yields a 1.5- to 5-fold improvement in extraction efficiency. The technique results in far less carryover of PCR inhibitors yielding analytical sensitivity improvements of over 25-fold. The combination of improved recovery and sensitivity make possible the detection of rare epigenetic events and the development of high sensitivity epigenetic diagnostic assays.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3217,

title = {Universal digital high-resolution melt: a novel approach to broad-based profiling of heterogeneous biological samples},

author = { S. I. Fraley and J. Hardick and B. J. Masek and P. Athamanolap and R. E. Rothman and C. A. Gaydos and K. C. Carroll and T. Wakefield and T. H. Wang and S. Yang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23935121},

doi = {10.1093/nar/gkt684},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2013},

date = {2013-10-01},

journal = {Nucleic Acids Res},

volume = {41},

number = {18},

pages = {e175},

abstract = {Comprehensive profiling of nucleic acids in genetically heterogeneous samples is important for clinical and basic research applications. Universal digital high-resolution melt (U-dHRM) is a new approach to broad-based PCR diagnostics and profiling technologies that can overcome issues of poor sensitivity due to contaminating nucleic acids and poor specificity due to primer or probe hybridization inaccuracies for single nucleotide variations. The U-dHRM approach uses broad-based primers or ligated adapter sequences to universally amplify all nucleic acid molecules in a heterogeneous sample, which have been partitioned, as in digital PCR. Extensive assay optimization enables direct sequence identification by algorithm-based matching of melt curve shape and Tm to a database of known sequence-specific melt curves. We show that single-molecule detection and single nucleotide sensitivity is possible. The feasibility and utility of U-dHRM is demonstrated through detection of bacteria associated with polymicrobial blood infection and microRNAs (miRNAs) associated with host response to infection. U-dHRM using broad-based 16S rRNA gene primers demonstrates universal single cell detection of bacterial pathogens, even in the presence of larger amounts of contaminating bacteria; U-dHRM using universally adapted Lethal-7 miRNAs in a heterogeneous mixture showcases the single copy sensitivity and single nucleotide specificity of this approach.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3219,

title = {A multiphase fluidic platform for studying ventilator-induced injury of the pulmonary epithelial barrier},

author = { D. D. Nalayanda and W. B. Fulton and T. H. Wang and F. Abdullah},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23835753},

doi = {10.1039/c3ib40037a},

issn = {1757-9708 (Electronic) 

1757-9694 (Linking)},

year  = {2013},

date = {2013-09-01},

journal = {Integr Biol (Camb)},

volume = {5},

number = {9},

pages = {1141-8},

abstract = {Mechanical ventilation has been a critical part of basic life support for many years, with almost one-third of all patients in the intensive care unit requiring the aid. However studies over the past two decades have indicated that ventilators have the potential to cause or aggravate pulmonary injury. The lung with its anatomically complex architecture and unique amalgam of cell types and interfaces is very difficult to replicate in vitro. This study is focused on mimicking the distal unit of the alveolus in developing an analytical platform for evaluating cellular interactions and response to mechanostimulation. The prototype developed incorporates the ability to expose alveolar cells to sustained periods of supra-physiological pressure when cultured at an air-liquid interface with constant air-flow on the apical side and medium replenishment on basolateral surfaces. The in vitro evaluation of the alveolar, A549 and H441, cells indicated disruption of the cell layer integrity in response to sustained pressure application. The results indicate a magnitude- and duration-dependent response among both the cell types.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3222,

title = {Micro and nanotechnologies enhanced biomolecular sensing},

author = { T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25586258},

doi = {10.3390/bios3030283},

issn = {2079-6374 (Print) 

2079-6374 (Linking)},

year  = {2013},

date = {2013-07-05},

journal = {Biosensors (Basel)},

volume = {3},

number = {3},

pages = {283-5},

abstract = {This editorial summarizes some of the recent advances of micro and nanotechnology-based tools and devices for biomolecular detection. These include the incorporation of nanomaterials into a sensor surface or directly interfacing with molecular probes to enhance target detection via more rapid and sensitive responses, and the use of self-assembled organic/inorganic nanocomposites that inhibit exceptional spectroscopic properties to enable facile homogenous assays with efficient binding kinetics. Discussions also include some insight into microfluidic principles behind the development of an integrated sample preparation and biosensor platform toward a miniaturized and fully functional system for point of care applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3221,

title = {Full-range magnetic manipulation of droplets via surface energy traps enables complex bioassays},

author = { Y. Zhang and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23529938},

doi = {10.1002/adma.201300383},

issn = {1521-4095 (Electronic) 

0935-9648 (Linking)},

year  = {2013},

date = {2013-06-04},

journal = {Adv Mater},

volume = {25},

number = {21},

pages = {2903-8},

abstract = {Manipulating droplets on an open surface promises an easier, more flexible, and more scalable platform of liquid control, than does microchannel-based fluidics. In this report, a surface-energy-trap-enabled magnetic droplet handling platform is introduced that is capable of comprehensive droplet manipulations, including droplet dispensing, transport, fusion, and particle extraction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3223,

title = {Single quantum dot analysis enables multiplexed point mutation detection by gap ligase chain reaction},

author = { Y. Song and Y. Zhang and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23239594},

doi = {10.1002/smll.201202242},

issn = {1613-6829 (Electronic) 

1613-6810 (Linking)},

year  = {2013},

date = {2013-04-08},

journal = {Small},

volume = {9},

number = {7},

pages = {1096-105},

abstract = {Gene point mutations present important biomarkers for genetic diseases. However, existing point mutation detection methods suffer from low sensitivity, specificity, and a tedious assay processes. In this report, an assay technology is proposed which combines the outstanding specificity of gap ligase chain reaction (Gap-LCR), the high sensitivity of single-molecule coincidence detection, and the superior optical properties of quantum dots (QDs) for multiplexed detection of point mutations in genomic DNA. Mutant-specific ligation products are generated by Gap-LCR and subsequently captured by QDs to form DNA-QD nanocomplexes that are detected by single-molecule spectroscopy (SMS) through multi-color fluorescence burst coincidence analysis, allowing for multiplexed mutation detection in a separation-free format. The proposed assay is capable of detecting zeptomoles of KRAS codon 12 mutation variants with near 100% specificity. Its high sensitivity allows direct detection of KRAS mutation in crude genomic DNA without PCR pre-amplification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3224,

title = {Discerning single molecule interactions of DNA and quantum dots},

author = { T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23097334},

doi = {10.1002/biot.201200309},

issn = {1860-7314 (Electronic) 

1860-6768 (Linking)},

year  = {2013},

date = {2013-01-01},

journal = {Biotechnol J},

volume = {8},

number = {1},

pages = {15-6},

abstract = {Measurements of interactions between nanoparticles and DNA at the molecular level offer insight to the rationale design of nano-complexes for biomedical imaging and sensing. This commentary describes the work of Kungang Li and colleagues, who report a study of atomic force microscopy-enabled single molecule imaging of quantum dots and DNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3227,

title = {PDMS-glass bonding using grafted polymeric adhesive--alternative process flow for compatibility with patterned biological molecules},

author = { C. W. Beh and W. Zhou and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/22858861},

doi = {10.1039/c2lc40315c},

issn = {1473-0189 (Electronic) 

1473-0189 (Linking)},

year  = {2012},

date = {2012-10-21},

journal = {Lab Chip},

volume = {12},

number = {20},

pages = {4120-7},

abstract = {We report a novel modification of silicone elastomer polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between an elastomer and glass substrate to be performed without exposure of the substrate to harsh treatment conditions, such as oxygen plasma. Organic molecules can thus be patterned within microfluidic channels and still remain functional post-bonding. In addition, after polymer grafting the PDMS can be stored in a desiccator for at least 40 days, and activated upon exposure to acidic buffer for bonding. The bonded devices remain fully bonded in excess of 80 psi driving pressure, with no signs of compromise to the bond integrity. Finally, we demonstrate the compatibility of our method with biological molecules using a proof-of-concept DNA sensing device, in which fluorescently-labelled DNA targets are successfully captured by a patterned probe in a device sealed using our method, while the pattern on a plasma-treated device was completely destroyed. Therefore, this method provides a much-needed alternative bonding process for incorporation of biological molecules in microfluidic devices.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3226,

title = {A serial sample loading system: interfacing multiwell plates with microfluidic devices},

author = { T. D. Rane and H. C. Zec and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/22885789},

doi = {10.1177/2211068212455169},

issn = {2211-0690 (Electronic) 

2211-0682 (Linking)},

year  = {2012},

date = {2012-10-01},

journal = {J Lab Autom},

volume = {17},

number = {5},

pages = {370-7},

abstract = {There is an increasing demand for novel high-throughput screening (HTS) technologies in the pharmaceutical and biotechnological industries. The robotic sample-handling techniques currently used in these industries, although fast, are still limited to operating in multiwell plates with the sample volumes per reaction in the microliter regime. Digital microfluidics offers an alternative for reduction in sample volume consumption for HTS but lacks a reliable technique for transporting a large number of samples to the microfluidic device. In this report, we develop a technique for serial delivery of sample arrays to a microfluidic device from multiwell plates, through a single sample inlet. Under this approach, a serial array of sample plugs, separated by an immiscible carrier fluid, is loaded into a capillary and delivered to a microfluidic device. Similar approaches have been attempted in the past, however, either with a slower sample loading device such as a syringe pump or vacuum-based sample loading with limited driving pressure. We demonstrated the application of our positive-pressure-based serial sample loading (SSL) system to load a series of sample plugs into a capillary. The adaptability of the SSL system to generate sample plugs with a variety of volumes in a predictable manner was also demonstrated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3228,

title = {Droplet microfluidics for amplification-free genetic detection of single cells},

author = { T. D. Rane and H. C. Zec and C. Puleo and A. P. Lee and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/22842841},

doi = {10.1039/c2lc40537g},

issn = {1473-0189 (Electronic) 

1473-0189 (Linking)},

year  = {2012},

date = {2012-09-21},

journal = {Lab Chip},

volume = {12},

number = {18},

pages = {3341-7},

abstract = {In this article we present a novel droplet microfluidic chip enabling amplification-free detection of single pathogenic cells. The device streamlines multiple functionalities to carry out sample digitization, cell lysis, probe-target hybridization for subsequent fluorescent detection. A peptide nucleic acid fluorescence resonance energy transfer probe (PNA beacon) is used to detect 16S rRNA present in pathogenic cells. Initially the sensitivity and quantification abilities of the platform are tested using a synthetic target mimicking the actual expression level of 16S rRNA in single cells. The capability of the device to perform "sample-to-answer" pathogen detection of single cells is demonstrated using E. coli as a model pathogen.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3229,

title = {Microfluidic platform for on-demand generation of spatially indexed combinatorial droplets},

author = { H. Zec and T. D. Rane and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/22810353},

doi = {10.1039/c2lc40399d},

issn = {1473-0189 (Electronic) 

1473-0189 (Linking)},

year  = {2012},

date = {2012-09-07},

journal = {Lab Chip},

volume = {12},

number = {17},

pages = {3055-62},

abstract = {We propose a highly versatile and programmable nanolitre droplet-based platform that accepts an unlimited number of sample plugs from a multi-well plate, performs digitization of these sample plugs into smaller daughter droplets and subsequent synchronization-free, robust injection of multiple reagents into the sample daughter droplets on-demand. This platform combines excellent control of valve-based microfluidics with the high-throughput capability of droplet microfluidics. We demonstrate the functioning of a proof-of-concept device which generates combinatorial mixture droplets from a linear array of sample plugs and four different reagents, using food dyes to mimic samples and reagents. Generation of a one dimensional array of the combinatorial mixture droplets on the device leads to automatic spatial indexing of these droplets, precluding the need to include a barcode in each droplet to identify its contents. We expect this platform to further expand the range of applications of droplet microfluidics to include applications requiring a high degree of multiplexing as well as high throughput analysis of multiple samples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN3225,

title = {Quantum dot enabled molecular sensing and diagnostics},

author = { Y. Zhang and T. H. Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/22916072},

doi = {10.7150/thno.4308},

issn = {1838-7640 (Electronic) 

1838-7640 (Linking)},

year  = {2012},

date = {2012-08-24},

journal = {Theranostics},

volume = {2},

number = {7},

pages = {631-54},

abstract = {Since its emergence, semiconductor nanoparticles known as quantum dots (QDs) have drawn considerable attention and have quickly extended their applicability to numerous fields within the life sciences. This is largely due to their unique optical properties such as high brightness and narrow emission band as well as other advantages over traditional organic fluorophores. New molecular sensing strategies based on QDs have been developed in pursuit of high sensitivity, high throughput, and multiplexing capabilities. For traditional biological applications, QDs have already begun to replace traditional organic fluorophores to serve as simple fluorescent reporters in immunoassays, microarrays, fluorescent imaging applications, and other assay platforms. In addition, smarter, more advanced QD probes such as quantum dot fluorescence resonance energy transfer (QD-FRET) sensors, quenching sensors, and barcoding systems are paving the way for highly-sensitive genetic and epigenetic detection of diseases, multiplexed identification of infectious pathogens, and tracking of intracellular drug and gene delivery. When combined with microfluidics and confocal fluorescence spectroscopy, the detection limit is further enhanced to single molecule level. Recently, investigations have revealed that QDs participate in series of new phenomena and exhibit interesting non-photoluminescent properties. Some of these new findings are now being incorporated into novel assays for gene copy number variation (CNV) studies and DNA methylation analysis with improved quantification resolution. Herein, we provide a comprehensive review on the latest developments of QD based molecular diagnostic platforms in which QD plays a versatile and essential role.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}